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Comparison of Genes in Imiquimod-treated and Control Tumors

ABSTRACT: The goal of the study is to examine changes in tumor gene expression after imiquimod treatment. RNA was extracted from spontaneous tumors in control mice (n=4) and in imiquimod-treated mice (n=4). Gene expression was compared between the control group and the treated group. In the imiquimod treatment group, the mice received topical treatment of 5% imiquimod cream (Aldara) on shaved skin at the site of spontaneous tumors for one treatment cycle (3 consecutive days). RNA was extracted from 4 spontaneous tumors from neu-tg mice treated with topical imiquimod for 1 cycle and 4 spontaneous tumors from control mice

ORGANISM(S): Mus musculus

SUBMITTER: Hangjun Duan

PROVIDER: E-GEOD-20032 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Treatment failure of a TLR-7 agonist occurs due to self-regulation of acute inflammation and can be overcome by IL-10 blockade.

Lu Hailing H Wagner Wolfgang M WM Gad Ekram E Yang Yi Y Duan Hangjun H Amon Lynn M LM Van Denend Nathaniel N Larson Emily R ER Chang Amy A Tufvesson Helena H Disis Mary L ML

Journal of immunology (Baltimore, Md. : 1950) 20100322 9

Multiple TLR agonists have been shown to have antitumor effects in animal models. However, the therapeutic efficacy of TLR agonist monotherapy in cancer treatment has been limited, and the mechanisms of failure remain unknown. We demonstrate that topical treatment with a TLR-7 agonist, imiquimod, can elicit significant regression of spontaneous breast cancers in neu transgenic mice, a model of human HER-2/neu(+) breast cancer. However, tumor growth progressed once imiquimod therapy was ended. Ge ...[more]

PMID: 20308630

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Comparison of Genes in Imiquimod-treated and Control Tumors

Project description:The goal of the study is to examine changes in tumor gene expression after imiquimod treatment. RNA was extracted from spontaneous tumors in control mice (n=4) and in imiquimod-treated mice (n=4). Gene expression was compared between the control group and the treated group. In the imiquimod treatment group, the mice received topical treatment of 5% imiquimod cream (Aldara) on shaved skin at the site of spontaneous tumors for one treatment cycle (3 consecutive days).

2010-01-26 | GSE20032 | GEO

Expression data from Imiquimod-induced psoriasis mouse model

Project description:Psoriasis is a chronic inflammatory skin disorder that is predominantly characterized by sharply demarcated chronic erythematous plaques. Although its etiological mechanisms are largely unknown, recent evidence suggests that the topical application of imiquimod (IMQ) cream causes psoriasis-like skin inflammation in humans and mice. Skin examined 4 hours after IMQ cream treatment. Results provide insight into the role of each knockout mice phenotype in the response to IMQ-induced psoriasis model.

2017-10-06 | GSE104603 | GEO

Expression data from IMQ-induced psoriasis-like skin inflammation in miR-146a-/- and C57BL6J mice

Project description:miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara). Gene expression profiling (Affymetrix) was used to identify transcriptomic changes associated with psoriasis-like skin inflammation in wild type vs. miR-146a -/-mice. A daily topical dose of 31.25 mg of Aldara cream (5% IMQ) was applied on the right ear of miR-146a -/- and C57BL/6 mice on three consecutive days to induce psorisis-like skin inflammation. Mice were sacrificed at day 4. Ear flaps were collected for total RNA extraction and hybridization on Affymatrix GeneTitan plate format Gene ST 2.1 (mouse).

2016-02-19 | E-GEOD-78057 | biostudies-arrayexpress

Epigenetic silencing of SFRP4 contributes to epidermal hyperplasia in psoriasis

Project description:To investigate the gene expression of imiquimod induced psoriasis-like mouse model, we have employed whole genome microarray as a discovery platform to identify genes differentially expressed compared with wild type C57BL6 mouse exposed to the vehicle of imiquimod. C57BL/6J mice at 6 to 8 weeks of age were applied to a daily topical dose of 62.5 mg of IMQ cream (5%) on the shaved back for 7 consecutive days. Control mice were treated with a same dose of vehicle cream.The total RNA was extracted by using TRIzol.

2014-08-28 | E-GEOD-60804 | biostudies-arrayexpress

Expression data from IMQ-induced psoriasis-like skin inflammation in miR-146a-/- and C57BL6J mice

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Microarray analysis of the brain response to cutaneous Aldara treatment

Project description:Analysis of whole mouse brain following peripheral, cutaneous immune stimulation with Aldara cream or aquaeous control cream. Results provide insight into the central response to peripheral inflammation Microarrays were used to investigate the global gene expression of mouse brains following peripheral, cutaneous application of Aldara cream or control cream C57BL/6 mice were treated with 80mg topical Aldara cream or aquaeous control cream every 24 hours for 5 consecutive days. 24 hours following the final application, brains were removed and RNA was extracted using RNeasy Mini Kit (Qiagen). 5 brains from each group were analysed using full genome Affymetrix GeneChip array

2016-08-19 | E-GEOD-72214 | biostudies-arrayexpress

Vaccination and topical imiquimod treatment promote immune signatures in melanoma

Project description:Introduction: Infiltration of cancers by T-cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T-cell infiltration of tumors are not known. This study tests the hypothesis that topical treatment of melanoma metastases with the TLR7 agonist imiquimod treatment plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and Methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to tumors daily. Adverse events (AE; CTCAE v4.03) were recorded and effects on the tumor microenvironment (TME) were evaluated from sequential tumor biopsies. T-cell responses were assessed by IFNgamma ELIspot assay, and T-cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and Conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination was well tolerated in these patients. Circulating T-cell responses to the vaccine were detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T-cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. Precis: This clinical trial tested topical application of imiquimod to melanoma metastases combined with a melanoma vaccine. The regimen dramatically upregulated immune rejection gene signatures in melanoma metastases and increased T-cell infiltrate.

2017-04-01 | GSE80028 | GEO

Topical Application of Nano-sized Graphene Oxide Cream Ameliorates Acute Skin Inflammation in Mice

Project description:We have previously shown that nano-sized graphene oxide (NGO) displays anti-inflammatory activities against natural killer T (NKT) cell-mediated sepsis. To address whether NGO could be applied to treat acute skin inflammation. We developed a conventional skin Cetaphil® cream containing NGO (NGO cream) for topical application to skin lesions and investigated its therapeutic efficacy by employing the tape-stripping-induced acute skin inflammation model. Topical application of NGO cream to the wounded area significantly reduced skin lesions compared with the control cream. Moreover, NGO cream treatment prevented the tape-stripping-elicited infiltration of and IL1β production by skin neutrophils and dendritic cells (DCs). Furthermore, such anti-inflammatory effects of NGO cream were attributed to decreased infiltration of IL12-producing DCs and IFNγ-producing cells (e.g., CD4+ T, CD8+ T, γδ T, NK, and NKT cells) into the skin. In addition, topical NGO cream administration enhanced the expression of suppressive molecules such as FR4 on skin regulatory T cells. Through RNA sequencing analysis, we found that the preventive effect of NGO cream on acute skin inflammation may be correlated with the activation of keratinocytes located in the epidermis. Our results support NGO cream as a therapeutic option to control acute skin inflammation.

2024-08-20 | GSE272008 | GEO

A dietary oxysterol, 7-ketocholesterol, exacerbates imiquimod-induced psoriasis-like dermatitis in steatohepatitic mice (Liver)

Project description:Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. We previously identified an oxidized derivative of cholesterol, 7-ketocholesterol (7KC), in diet-induced steatohepatitic mice. Here, we investigated whether 7KC exacerbates psoriasis-like dermatitis by accelerating steatohepatitis in mice. A high fat/high cholesterol/high sucrose/bile salt diet (NASH diet) with or without 0.0125% 7KC was fed to C57BL/6 mice (7KC or control group) for three weeks to induce steatohepatitis. 5% imiquimod cream was then applied to the ears and dorsal skin for four days to induce psoriasis-like dermatitis. Hepatic lipid accumulation and inflammatory cell infiltration were exacerbated in the 7KC group compared with the control group after three weeks. Serum tumor necrosis factor-α (TNF-α) levels were also elevated in the 7KC group (108.5±9.8 vs. 83.1±13.1 pg/ml, p<0.005). Imiquimod cream increased the psoriasis area severity index (PASI) score in mice in the 7KC group (9.14±0.75 vs. 5.17±1.17, p<0.0001). Additionally, Tnfa, Il23a, Il17a, and Il22 mRNA levels in the dorsal lesion were significantly upregulated. Finally, Th17 cell differentiation and the TNF signaling pathway were enhanced in the dorsal lesions and liver of mice in the 7KC group. These data suggest that steatohepatitis and psoriasis are linked by a potent, diet-related factor.

2022-12-27 | GSE214836 | GEO

A dietary oxysterol, 7-ketocholesterol, exacerbates imiquimod-induced psoriasis-like dermatitis in steatohepatitic mice (Dorsal skin)

2022-12-27 | GSE214835 | GEO